Age-related macular degeneration (AMD) is a leading cause of blindness in United States and many other industrialized nations. There are two types of AMD, the dry and wet forms. Dry AMD is a chronic disease that usually causes variable degree of visual impairment. In contrast, in wet AMD, which affects ~10%-15% of AMD patients, the disease progresses rapidly to blindness if left untreated with severe lesions in Bruch's membrane and retinal pigment epithelium (RPE) layer and concomitant choroidal neovascularization (CNV). In the current standard of care, wet AMD patients receive anti-vascular endothelial growth factor (VEGF) agents. Although this therapy improves visual acuity in a substantial proportion of patients, most patients do not achieve substantial visual improvement and a third of treated eyes progress to legal blindness. Half of the eyes receiving VEGF experience persistent CNV leakage, fibrotic scarring and/or geographic atrophy. Further, frequent intravitreal injections represent a significant financial burden and entail risks that include pain, bleeding, infection, traumatic injury, and retinal tear, detachment and degeneration. A novel therapeutic strategy, which improves outcomes in a less invasive manner, reducing risk, while providing long-term inhibition of angiogenesis with acceptable safety profile, is an urgent and unmet medical need. iVeena has developed and patented (US Patent No. 8,211,864 B2) an intracellular anti-angiogenic therapy relying on expression of Flt23k intraceptors, selectively, at the lesions of Bruch's/RPE and choroid to sequester VEGF from secretion and also prevent intracellular autocrine loops. Our early research has demonstrated that a single intravenous dose of Flt23k intraceptors nanoparticles inhibits laser-induced CNV in mice, rat and monkey CNV models without major side effects. This early research is attracting the attention of the marketplace. Novartis in Cambridge, MA has requested sample materials from iVeena to explore the efficacy of Flt23k nanoparticles in their in-house CNV models (Please see the attached Material Transfer Agreement between iVeena and Novartis). With SBIR funding, iVeena is planning to further develop this novel approach. The specific aims of this Phase I SBIR project are: ? Aim 1 - To perform a Flt23k nanoparticle dose-ranging study ? Aim 2 - Establish the safety of the treatment All the proposed studies will be performed using the established laser-induced CNV model in mice. The successful completion of these studies will identify a safe and efficacious therapeutic dose that is feasible for manufacturing under GMP conditions to test in higher primates for proof-of-concept (POC) studies in Phase II application of this project.